SEB is one of enterotoxins (causative toxins of toxin-type food poisoning) produced by Staphylococcus aureus. SEB consists of 239 amino acid residues and its amino acid sequence is known (SEQ ID NO: 1). The SEB molecule comprises two domains, the first domain consisting of residues 1 to 120, and the second domain consisting of residues 127 to 239.
Staphylococcus aureus is indigenous bacteria. On the other hand, it is also known that infections caused by Staphylococcus aureus resistant to many antibiotics are extremely severe and have no good prognosis. Serious Staphylococcal infections, typically food poisoning, are mainly caused by toxins released out of the bacterial cells. Among such toxins, Staphylococcal enterotoxin (hereinafter also referred to as “SE”) is a kind of superantigens and acts on a number of T lymphocytes to cause them to extensively produce inflammatory cytokines that would never occur under normal conditions (Non-patent reference 1). The action of extensive inflammatory cytokines causes shock-like symptoms which may lead the organism to death. It is reported that in healthy adults a proportion of those who possess an antibody to Staphylococcal enterotoxin (SE) becomes higher with age (Non-patent reference 2). Under immunodeficient conditions such as a terminal stage of malignant tumors, however, it is supposed that patients would be more likely to allow for invasion of drug-resistant Staphylococcus aureus to thereby undergo inflammation due to Staphylococcal enterotoxin B (SEB).
It is reported that a high proportion of atopic patients has an IgE type anti-SEB antibody and hence correlation between SEB and pathological conditions of atopic diseases is suspected (Non-patent reference 3).
Also, in case of rheumatoid patients, epidemiological data suggesting correlation between SEB and onset or pathological conditions of rheumatoid diseases are reported and association of an IgM type anti-SEB antibody with pathological conditions of rheumatoid diseases is reported (Non-patent reference 4).
Epidemiologically, it is reported that in human a proportion of those who possess an antibody against SEB increases with age with that of adults not less than 7 years old being almost 100% (Non-patent reference 5).
However, in general, an antibody titer of the antibody against SEB is not so high and it is not known whether said antibody has affinity sufficient for neutralization of SEB in blood.
On the other hand, for the purpose of prevention and treatment of various diseases associated with SEB such as food poisoning, there are many reports of modified SEB with decreased toxicity (Non-patent reference 6). The present inventors have also prepared modified SEB with much reduced toxicity and confirmed that said modified SEB maintained an ability to induce antibody production as SEB (SEB variant wherein the asparagine residue at 23-position is replaced with the tyrosine residue; Patent reference 1).
However, the conventional modified SEBs including those of the present inventors, though having a reduced toxicity, may still be able to activate human lymphocytes at a concentration of several ten ng/ml, which still needs be improved from the viewpoint of toxicity of a vaccine antigen.
There is a report on a modified SEB in which a contact region with MHC is modified, one in which a contact region with TCR is modified, and the like, based on conformational analysis of the SEB structure (Non-patent reference 7).    Patent reference 1: WO99/40935 pamphlet    Non-patent reference 1: v. v. Micusan and J. Thibodeau, “Seminars in Immunology”, 1993, Vol. 5, p. 3-11    Non-patent reference 2: Kuwahata, M. et al., “Acta Pediatrica Japonica”, 1996, 38, p. 1-7    Non-patent reference 3: Sohn M H., Kim G H, Kim W K, Jang G C, Kim K E, “Allergy Asthma Proc.”, 2003, 24(1), p. 67-71    Non-patent reference 4: Origuchi T., Eguchi K., Kawabe Y., Yamashita I., Mizokami A., Ida H., Nagataki S., “Ann. Rheum. Dis.”, 1995, 54(9), p. 713-720    Non-patent reference 5: Kuwahata, M., Imanaka, H., Takei, S, and Masuda, K., “Acta Oediatrica Japonica”, 1996, 38, p. 1-7    Non-patent reference 6: Woody M A, Krakauer T, Stiles B G, “Vaccine”, 1997, 15(2), p. 133-139    Non-patent reference 7: Leder L. et al., “Journal of Experimental Medicine”, 1998, 187(6), p. 823-833